Clinical trials

Challenge: A client had achieved approval for a Phase 2 clinical trial, but during review of stability data observed an increase in a degradation product trending towards an out of specification result before the end of the trial period. The trial was due to start one month later, and there was not sufficient time or resource to manufacture another batch.

Solution: The impurity was evaluated to understand the toxicity profile at the increased level and a substantial amendment submitted to widen the impurity limit, supported by a justification that the impurity had very low toxicity. The amendment was submitted and approved within 3 weeks, allowing the trial to start on time, with the proposed batch.

Insight: It is always worth asking the Regulators. A well presented case can often be accepted.

Challenge: A client had received a Request for Information following an MAA submission, including questions related to the validation of the sterile drug substance manufacturing process, of which full details had been provided in the dossier. Support was requested in preparing the responses to the questions.

Solution: Responses were authored with the view that this information is neither required nor should have been presented, and to reassure the assessor that this was an error during submission.
All points were resolved during the first round of assessment.

Insight: Knowing what information to provide is key, but admitting any oversights early on can save a lot of justification and future questions.

Authoring MAAs and RtQs

Scientific Advice

Challenge: A client developed a new fixed dose combination product for two unrelated conditions, intending to submit through the Decentralised procedure. Scientific advice was recommended in two EU member states to discuss the data and approach, prior to completion of phase 3 trials. One member state could not accept the use of Article 10.b of Directive 2001/83/EC as amended on the basis that the indications were not related, however a second member state was persuaded to consider an application based on demonstrated patient benefits.

Solution: The regulatory strategy was updated to a National license application followed by roll out through the Mutual Recognition Procedure.

Insight: Selection of the most appropriate legal basis and MAA procedure, and early engagement of Regulatory authorities is the foundation of a smooth path to success.

Challenge: A global pharmaceutical company had reformulated a well known family consumer healthcare product, which resulted in increased impurity levels during shelf life. The shelf presence was critical as any out of stock situations would have resulted in a proportion of customers switching to another brand, and not returning. The client had prepared a Type II variation to widen the impurity limits, estimating 8 months between variation preparation and approval.

Solution: An alternative strategy of submitting a Type 1B variation to shorten the shelf life was proposed. Individual Authorities were contacted to request expedited assessment and the variation was prepared, submitted and approved within 5 days, thus preventing an out of stock situation in 4 EU markets.

Insight: There are often several solutions available. Selecting the best one for your product is key.

Life Cycle Maintenance